This invention relates to the preparation of tablets comprising acetaminophen. In general, there are four principle methods widely used in the United States for tablet manufacture. The four methods are:
Direct Compression--In this method, all required tableting aids are incorporated in a free flowing granulation as supplied by the bulk analgesic manufacturer. The granulation requires no pre-processing, or blending with additional aids, and is charged directly to a tableting press. This method is used extensively in the manufacture of generic aspirin tablets. PA1 Dry Powder Blend--In this method all required tableting aids are blended with crystal grade acetaminophen or aspirin. The blend is then charged directly to a tableting press. Gelatin or polyvinylpyrrolidone coated acetaminophen powder is sometimes used in place of crystal grade acetaminophen. PA1 Pre-Compressed Dry Powder Blend--In this method the dry powder blend containing all required tableting aids is pre-compressed either by roll compaction or slugging. Roll compaction is the most popular method of preparing granulated aspirin. A homogenous blend of aspirin and starch is roll compacted, milled, sifted and drummed. The granulated product is charged directly to a tableting press. PA1 Wet Granulation--This is the most popular method of granulating acetaminophen. In this method acetaminophen crystal or powder is blended with intragranular excipients, then wetted to a moist powder consistency with an aqueous binder solution. In some cases the powder is wetted to a dough consistency and forced through a 10-14 mesh screen. The wetted mass is then dried by conventional means, milled, sifted, and blended with extragranular excipients and lubricant. This mixture is then fed to a tableting press.
Acetaminophen is not ordinarily amenable to tableting by the same methods as aspirin. These materials have significantly different properties. Thus, crystalline aspirin is easily tableted, since the crystals are quite soft and exhibit good plasticity/elasticity when compacted to tablets. Further, cohesive/adhesive bonding within the aspirin tablet is strong and the aspirin, itself, provides good lubricity to the formula. Accordingly, no lubricant is necessary in the formula used for aspirin tableting. In contrast, acetaminophen crystals are very hard and brittle and fracture very easily. The crystals have essentially no plasticity/elasticity and can be tableted by the normal aspirin tableting methods only by using high levels of excipients and large crystalline grade acetaminophen. Furthermore, at least 25% or more excipients are required in addition to high levels of lubricant. The large acetaminophen crystals have the disadvantage of being slowly dissolved in the body and require additional tableting aids to increase the rate of dissolution.
Accordingly, acetaminophen has been preferably tableted using the wet granulation method since the direct compression method, the dry powder blending method and the pre-compression method have not been shown to be amenable in acetaminophen tableting for the reasons noted above.
The direct compression method of preparing tablets would be the method of choice for preparing acetaminophen tablets if a formulation comprising acetaminophen could be prepared which would allow the use of such method. Accordingly, there is a need for an acetaminophen formulation containing all required tableting aids which may be used in direct compression tableting.